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RACP Written 2018 > Cardiology - Lipids > Flashcards

Cardiology - Lipids Flashcards

1
Q

What is the role of apolipoproteins?

A

Activate enzymes needed for lipoprotein metabolism

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2
Q

What is the function of apoprotein component of lipoproteins?

A

Structural support
Receptor recognition
Enzymatic activity

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3
Q

Where is ApoB-100 made?

A

In the liver

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4
Q

Where is ApoB-48 made?

A

In the intestine

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5
Q

What is Apo-AI?

A

The major protein in HDL that has been inversely correlated with arteriographic evidence of coronary disease

it activates the enzyme lecithin-cholesterol acyltransferase (LCAT)

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6
Q

What does LCAT (lecithin-cholesterol acyltransferase) do?

A

allows the HDL particle to convert cholesterol obtained from peripheral tissues to cholesterol ester

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7
Q

What is Apo-B 100

A

The primary apoprotein of LDL which allows recognition of the particle by the LDL receptors on cell surfaces

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8
Q

What are the genes that synthesise Apo-B48 and Apo-B 100

A

Trick question. They are made by the same gene.

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9
Q

Where is Apo-E found?

A

In VLDL particles AND in chylomicrons, IDLs and HDLs.

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10
Q

What does ApoE do?

A

ApoE helps remove chylomicrons from the serum to the liver

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11
Q

What is the characteristic pathology of Type III hyperlipoproteinaemia?

A

Most Type III hyperlipoproteinaemia patients are homozygous to apoprotein E2/2 genotype

Characterised by premature atherosclerosis
(BOTH hyperchol and hypertriglyceridaemia)

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12
Q

SECONDARY causes of VLDL overproduction

A

Excessive VLDL secretion by liver is seen in:

  • high carb diets
  • alcohol
  • obesity
  • nephrotic syndrome
  • cushing’s syndrome
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13
Q

What are the two PRIMARY causes of excessive VLDL production by the liver?

A

Familial combined hyperlipidaemia (FCHL)

Lipodystrophy

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14
Q

What are the features of Familial Combined Hyperlipidaemia (FCHL)?

A
  • elevated TG and LDL-C
  • low HDL
  • Cause of hyperlipidaemia in 20% of those with IHD <60yrs old
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15
Q

What are the features of lipodystrophy?

A
  • Truncal adiposity with decreased fat in buttocks and extremities
  • insulin resistance and T2DM
  • hepatosteatosis
  • elevated TG and LDL-C
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16
Q

What are the PRIMARY causes of impaired lipolysis of TG-rich lipoprotein (with VERY HIGH triglycerides)?

A 
Familial chylomicronaemia syndrome
Familial hypertriglyceridaemia (FHTG)
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17
Q

Features of Familial chylomicronaemia syndrome

A

PROFOUNDLY elevated chylomicrons
Fasting TG VERY high

Recurrent pancreatitis
Lipaemia retinalis
Xanthomas
Hepatosplenomegaly

** NOT associated with coronary artery disease **

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18
Q

What is the inheritance of the two types of familial chylomicronaemia syndrome?

A

LPL deficiency: Autosomal Recessive

Apo-C II Deficiency: Autosomal Recessive

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19
Q

What are the features of familial hypertriglyceridaemia (FHTG)?

A

ELEVATED fasting TG
Average/low LDL-C
Low HDL-C

NOT ELEVATED APO-B
NOT ASSOC. WITH CAD

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20
Q

What are the dyslipidaemias caused by impaired hepatic uptake of ApoB-containging lipoproteins?

A

Type 3 Hypercholesterolaemia
Sitosterolemia
Cholesterol Ester Storage Disease

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21
Q

What is Type 3 Hypercholesterolaemia?

A

aka Autosomal Dominant Hypercholesterolaemia due to Mutations in PCSK9

dyslipidaemia caused by impaired hepatic uptake of ApoB-containging lipoproteins

  • autosomal dominant
  • rare
  • responds well to PCSK9 inhibition
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22
Q

What mutation causes Type 3 Hypercholesterolaemia?

A

Mutation in PCSK9

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23
Q

What is Sitosterolaemia?

A

rare, autosomal recessive

dyslipidaemia caused by impaired hepatic uptake of ApoB-containging lipoproteins

Mutations in ATP-Binding Cassette (ABCG5 and ABCG8)
ALSO get anisocytosis, poikilocytosis and splenomegaly
–> respond VERY WELL to dietary modification and ezetimibe

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24
Q

What mutation causes Sitosterolaemia?

A

Mutations in ATP-Binding Cassette (ABCG5 and ABCG8)

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25
Q

What is Cholesterol Ester Storage Disease?

A

aka Lysosomal Acid Lipase Deficiency

dyslipidaemia caused by impaired hepatic uptake of ApoB-containging lipoproteins

Autosomal recessive
Elevated LDL-C
Low HDL-C
FATTY liver
Non-obese
NOT insulin resistant
26
Q

What are the dyslipidaemias due to impaired hepatic Apo-B uptake?

A

Type 3 hyperlipoproteinaemia

= Familial Dysbetalipoproteinaemia (FDBL)

27
Q

What is Type 3 Hyperlipoproteinaemia?

A

aka Familial Dysbetalipoproteinaemia (FDBL)

dyslipidaemia due to impaired hepatic Apo-B uptake

Autosomal recessive
Mixed hyperlipidaemia
Usually due to mutation in ApoE gene (only ApoE2 and ApoE3

28
Q

What are the dyslipidaemias due to inherited low levels of Apo-B lipoproteins?

A

Abetalipoproteinaemia
Familial hyperbetalipoproteinaemia
PSCK9 Deficiency

29
Q

What is Abetalipoproteinaemia?

A

A dyslipidaemia due to inherited low levels of Apo-B lipoproteins

Rare autosomal recessive

Associated neuro:

  • loss of tendon reflexes
  • reduced lower limb vibration and proprioception
  • ataxia and spastic gait
  • pigmented retinopathy
30
Q

What are the dyslipidaemias due to impaired hepatic uptake of ApoB containing lipoproteins?

A

Secondary causes:

  • hypothyroidism
  • CKD

Primary causes:

  • Type 1 hypercholesterolaemia (= Familial Hypercholesterolaemia “FH”)
  • Type 2 hypercholesterolaemia (= Familial Defective APOB-100)
31
Q

What is Type 1 hypercholesterolaemia?

A

aka Familial Hypercholesterolaemia “FH”

A dyslipidaemia due to impaired hepatic uptake of ApoB containing lipoproteins

Features:

  • AUTOSOMAL DOMINANT
  • due to loss of function mutation in LDL receptor
  • NORMAL TG
  • elevated lipoprotein (a)
  • VERY HIGH risk coronary artery disease (needs statin and PCSK9 inhibitor)
  • liver transplant is also an option
32
Q

What is Type 2 Hypercholesterolaemia?

A

aka Familial Defective APOB-100

A dyslipidaemia due to impaired hepatic uptake of ApoB containing lipoproteins

Features:

  • AUTOSOMAL DOMINANT
  • NORMAL TG
  • ELEVATED LDL-C
  • increased risk CAD
33
Q

What are the treatment targets for 2013 ACC/AHA Guidelines?

A

No treatment targets

34
Q

When do you initiate primary prevention for hyperlipidaemia as per 2013 ACC/AHA Guidelines?

A

Age >21yrs with LDL-C >=4.9mmol/L

  • initiate high intensity statin
  • aim for AT LEAST 50% reduction in LDL-C
  • if the LDL-C remains >=4.9 despite maximum statin then add in a non-statin drug

If LDL-C level is 1.9 - 4.9mmol/L
WITH DIABETES:
- initiate statin age 40 - 75yrs
IF their 10yr ASCVD risk >=7.5% give high intensity
- IF they are <45yrs or >75yrs only CONSIDER a statin

IF LDL-C level is 1.9 - 4.9mmol/L
WITHOUT DIABETES:
- if aged 45-75yrs AND 10yr risk >=7.5% then start moderate or high intensity statin
- CONSIDER if age <45yrs or >75yrs

35
Q

According to the 2013 ACC/AHA Guidelines for primary prevention for hyperlipidaemia in age >21yrs with LDL-C >=4.9mmol/L

A
  • initiate high intensity statin
  • aim for AT LEAST 50% reduction in LDL-C
  • if the LDL-C remains >=4.9 despite maximum statin then add in a non-statin drug
36
Q

According to the 2013 ACC/AHA Guidelines for primary prevention for hyperlipidaemia
If LDL-C level is 1.9 - 4.9mmol/L
WITH DIABETES:

A
  • initiate statin age 40 - 75yrs
    IF their 10yr ASCVD risk >=7.5% give high intensity
  • IF they are <45yrs or >75yrs only CONSIDER a statin
37
Q

According to the 2013 ACC/AHA Guidelines for primary prevention for hyperlipidaemia
IF LDL-C level is 1.9 - 4.9mmol/L
WITHOUT DIABETES:

A
  • if aged 45-75yrs AND 10yr risk >=7.5% then start moderate or high intensity statin
  • CONSIDER if age <45yrs or >75yrs
38
Q

What are the HIGH intensity statins? When using them what do you aim for?

A

Aim to lower LDL-C by 50%

Atorvastatin 40 - 80mg
Rosuvastatin 20 - 40mg

39
Q

What are the MODERATE intensity statins? When using them what do you aim for?

A

Aim to lower LDL-C by 30 - 50%

Atorvastatin 10-20mg
Rosuvastatin 5-10mg
Simvastatin 20-40mg
Pravastatin 40-80mg
Lovastatin 40mg
Fluvastatin
40
Q

What is the MoA of statins?

A

Competitively inhibit 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase

(rate limiting step in cholesterol production)

41
Q

Common side effects of statins

A

Myopathy and rhabdo
Autoimmune necrotising myopathy
Sleep disturbance (insomnia and nightmares)
Elevated transaminases

42
Q

Rare side effects of statins

A 
Pancreatitis
Paraesthesias
Peripheral neuropathy and sexual dysfunction
Interstitial lung disease
Thrombocytopenia
43
Q

Benefits of statins?

A

Reduce risk MI
Reduce risk stroke
Reduce revascularity procedures
Mortality benefit

44
Q

Mechanism of action of cholestyramine?

A

Bile acid sequestrant/resin

Binds bile acids in intestinal lumen to prevent bile acid resorption

  • -> increased demand for cholesterol to be converted to bile acid synthesis
  • -> increases LDL uptake and removal from plasma
45
Q

Side effects of cholestyramine?

A

Exacerbates hyperTRIGLICERIDAEMIA (so avoid if TG >3mmol/L)

Avoid if complete biliary obstruction

Constipation
Aggravation of haemorrhoids and diverticulosis

Fat soluble vitamin deficiencies

46
Q

Benefits of cholestyramine?

A

Reduce LDL by 15-20%

Reduces risk of nonfatal MI/death secondary to CVS in men without heart disease and total cholesterol >6.8mmol/L

47
Q

Mechanism of action of Nicotinic Acid?

A

Suppresses fatty acid release from peripheral tissue especially adipose tissue

If dosed >1g daily:

  • Reduced LDL
  • Reduced Triglycerides
  • Elevated HDL
  • Reduced Lipoprotein (a)
48
Q

Side effects of Nicotinic Acid?

A

Peptic ulcer disease
GORD

In coronary artery disease it is associated with AF

Vasodilation (results in hypotension)

Macula oedema and reversible vision loss

49
Q

Benefits of Nicotinic Acid?

A 
Reduces total chol
Reduces LDL-C
Reduces triglycerides
Increases HDL-C
Reduces coronary artery disease
Reduces CVS events

NO MORTALITY BENEFIT

50
Q

What is the mechanism of action of Ezetimibe?

A

Reduces absorption of dietary and biliary cholesterol by inhibiting its transport across the intestine wall –> increases demand for cholesterol and increases LDL uptake

51
Q

Side effects of Ezetimibe?

A

Headache
Diarrhoea
Raised transamnases

52
Q

Benefits of Ezetimibe?

A

Reduces LDL by 18%

ONLY evidence is in combo with a statin

53
Q

Mechanism of action of Fibrates

A

Activate peroxisome activated nuclear receptors and modulate lipoprotein synthesis and catabolism

54
Q

Side effects of Fibrates

A 
GIT disturbance
Gallstones
Pancreatitis
Leukopenia
Myopathy
55
Q

Benefits of Fibrates

A

Reduce LDL by 5-15%
Greatest benefits if HDL <1 and TG>2.3

Reduces non-fatal MI
Reduces risk retinopathy
Reduces risk progression of albuminuria

NO EFFECT on MORTALITY

56
Q

What is PCSK9?

A

PCSK9 = Proprotein Convertase Subtilisin-Kexin Type 9

PCSK9 binds to LDL Receptor on hepatocytes to stimulate ingestion of the LDL-R with degradation of the LDL-R-PCSK9 complex.

Because of reduced numbers of LDL-R on surface there is higher blood levels of LDLs

57
Q

What do PSCK9 inhibitors do?

A

Bind to PCSK9 to stop it binding to LDL-R

58
Q

What are the names of the PCSK9 inhibitors?

A

Alirocumab
Evolocumab
Bococizumab

59
Q

What are the benefits of PCSK9 inhibitors?

A

Reduce major CVS events
Reduce lDL

Bococizumab reduces CVS events in high risk patients

60
Q

Neurocognitive adverse events are seen in which PCSK9 inhibitor?

A

Bococizumab

RACP Written 2018 (167 decks)

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